Mechanical factors have long been assumed to have a potent influence on the formation, maintenance and adaptation of bone. While numerous experimental and analytical studies have attempted to quantify the relationship between mechanical stimulation and bone adaptation, difficulties associated with controlling or monitoring boundary conditions during these experiments have limited their success. During the past funding cycle, significant progress has been made in controlling and quantifying the local environment associated with implant delivered load of trabecular bone. The focus of the current proposal is to begin to identify the cellular events associated with the morphologic and architectural adaptation of bone subjected to in vivo controlled load. The experimental model utilizes a unique large volume bone chamber which stimulates infiltration of new bone that can then be subjected to experimentally controlled loading histories through the incorporation of a hydraulically activated actuator within the chamber. The ability to repeatedly sample volumes of trabecular bone subjected experimentally determined loading conditions, coupled with digitally imaged based microstructural analytical models, will enable the investigators to make correlations between tissue and lamellar level stress and strain conditions and cellular responses. This model will begin to merge cellular and molecular measures developed for in vitro assays with the physiologic relevance of in vivo studies. Bone cellular biosynthetic activity and subsequent morphologic and architectural adaptation of the extracellular matrix will be evaluated both temporally and in response to variations in loading magnitude and loading rate.